Amyloid βprotein precursor in cultured leptomeningeal smooth muscle cells

Smooth muscle cell cultures were established from human leptomeningeal blood vessels obtained at autopsy from a patient with normal cortical blood vessels and a patient with extensive cerebral amyloid angiopathy (CAA). The normal leptomeningeal smooth muscle cells and CAA/ leptomeningeal smooth muscle cells were compared to normal human aorta smooth muscle cells with respect to amyloid βprotein precursor (AβPP) expression. All the cultured smooth muscle cells secreted a prominent =110 kDaform of AβPP that contained the Kunitz-type serine protease inhibitor domain analogous to protease nexin-2 (PN-2). Quantitative measurements revealed that aorta smooth muscle cells secrete -1.5-fold more PN-2/ABPP than normal leptomeningeal smooth muscle cells and CAA/ leptomeningeal smooth muscle cells. In contrast, the normal leptomeningeal smooth muscle cells and CAA/ leptomeningeal smooth muscle cells retain =2.4- and =3.3-fold, respectively, more cell-associated AβPP than aorta smooth muscle cells. These preliminary findings suggest that the decreased secretion of PN-2/AβPP observed in leptomeningeal smooth muscle cells compared to aorta smooth muscle cells may contribute to the formation of Aβ that is selectively deposited in the walls of cortical and leptomeningeal blood vessels.